M I San Andrés

Complutense University of Madrid, Madrid, Madrid, Spain

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Publications (48)57.82 Total impact

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    ABSTRACT: Enrofloxacin is widely used in veterinary medicine and is an important alternative to treating bacterial infections, which play an important role as causes of disease and death in captive snakes. Its extralabel use in nontraditional species has been related to its excellent pharmacokinetic and antimicrobial characteristics. This can be demonstrated by its activity against gram-negative organisms implicated in serious infectious diseases of reptile species with a rapid and concentration-dependent bactericidal effect and a large volume of distribution. Pharmacokinetic parameters for enrofloxacin were investigated in seven urutu pit vipers (Bothrops alternatus), following intramuscular injections of 10 mg/kg. The plasma concentrations of enrofloxacin and its metabolite, ciprofloxacin, were measured using high-performance liquid chromatography. Blood samples were collected from the ventral coccygeal veins at 0.5, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 108, and 168 hr. The kinetic behavior was characterized by a relatively slow absorption (time of maximal plasma concentration = 4.50 +/- 3.45 hr) with peak plasma concentration of 4.81 +/- 1.12 microg/ml. The long half-life during the terminal elimination phase (t1/2 lambda = 27.91 +/- 7.55 hr) of enrofloxacin after intramuscular administration, calculated in the present study, could suggest that the antibiotic is eliminated relatively slowly and/or the presence of a slow absorption in urutu pit vipers. Ciprofloxacin reached a peak plasma concentration of 0.35 microg/ml at 13.45 hr, and the fraction of enrofloxacin metabolized to ciprofloxacin was 13.06%. If enrofloxacin's minimum inhibitory concentration (MIC90) values of 0.5 microg/ml were used, the ratios AUC(e+c): MIC90 (276 +/- 67 hr) and Cmax(e+c): MIC90 (10 +/- 2) reach the proposed threshold values (125 hr and 10, respectively) for optimized efficacy and minimized resistance development when treating infections caused by Pseudomonas. The administration of 10 mg/kg of enrofloxacin by the i.m. route should be considered to be a judicious choice in urutu pit vipers against infections caused by microorganisms with MIC values < or = 0.5 microg/ml. For less susceptible bacteria, a dose increase and/or an interval reduction should be evaluated.
    Journal of Zoo and Wildlife Medicine 03/2014; 45(1):78-85. · 0.43 Impact Factor
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    ABSTRACT: 1. The objective of the study was to evaluate the comparative pharmacokinetic behaviour of enrofloxacin in adult ostriches after single and multiple intramuscular (IM) and subcutaneous (SC) administrations. In addition, tissue tolerance was evaluated. 2. Enrofloxacin was well absorbed, but showed a short permanence after both administration routes. After multiple dose administrations the maximum and minimum peak plasma concentrations were very similar for both routes, obtaining a steady state phase from the second dose that extended until the last evaluated administration. 3. There was no significant accumulation after multiple IM or SC doses; however, there were differences in a fluctuation index after multiple intramuscular administrations that could be related to muscle damage. 4. The different microbiological efficacy indicators (PK/PD indices) obtained, the pharmacokinetic behaviour and CK serum concentrations suggest that subcutaneous enrofloxacin administration of 15 mg/kg every 12 h produce and maintain an efficient concentration of antibiotic that is a safer and more effective therapeutic option than intramuscular administration.
    British Poultry Science 06/2013; 54(3):391-397. · 1.15 Impact Factor
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    ABSTRACT: The purpose of this study was to determine the pharmacokinetic profile of marbofloxacin in llamas following single IV, IM and SC administration of 5 mg/kg bw. To assess whether these routes could be an option for the administration of marbofloxacin in this specie and estimate efficacy predictors (PK/PD) from bibliographic MIC90 values. The principal pharmacokinetic parameters were Vss = 0.72 ± 0.22 L/kg, Cl = 0.09 ± 0.03 L/kg h (for IV administration), Cmax = 7.43 ± 1.28 μg/mL and 6.94 ± 2.19 μg/mL for IM and SC administration, respectively; t1/2λ = 9.16 ± 1.08 h, 8.47 ± 0.31 h and 6.26 ± 0.87 h and MRT = 7.30 ± 1.07 h, 8.21 ± 1.57 h and 8.27 ± 0.96 h for IV, IM and SC administrations, respectively. The values obtained for the pharmacokinetic parameters were not significantly different among routes of administration except Cmax, Vz and t1/2λ. The values obtained from the PK/PD indices were Cmax/MIC90 (12.4–32.3) and AUC0–24/MIC90 (105.7–178.52 h); taking into account these values, it was concluded that a IM or SC dose of 5 mg/(kg day) of marbofloxacin would be adequate in treating infections caused by susceptible bacteria with MIC < 0.44 μg/mL.
    Small Ruminant Research 07/2012; 106(1):64–69. · 1.12 Impact Factor
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    ABSTRACT: From a human safety perspective, the administration of ivermectin to food producing animal species entails potential risks related to the presence of drug residues in edible tissues, milk, and other derived products. The European Medicines Agency has established the maximum residue limits for ivermectin in the European Union, with values of 100 μg·kg(-1) in fat and liver and 30 μg·kg(-1) in kidney for all mammalian food producing species, in order to ensure that the amount of ivermectin that can be found in animal foodstuff is below dangerous levels for the consumers. According to these values, withdrawal periods after subcutaneous injection were recently established in the European Union (2009), in 49 days for products containing ivermectin as a single active substance or in combination with closantel, and in 66 days when combined with clorsulon. The marker residue for ivermectin was found to be H(2)B(1a), which is the major component of the parent compound. The tissue distribution of residues and the overall ratios of marker to total residues were generally similar in most species, and the highest concentrations of ivermectin residues were found in fat and liver with high levels also detected in injection site muscles. Ivermectin is not licensed for use in animals from which milk is produced for human consumption, however its extra-label use should be considered regarding human safety, due to its long persistence in milk and milk-derived products.
    Current pharmaceutical biotechnology 10/2011; 13(6):987-98. · 3.40 Impact Factor
  • Journal of Veterinary Pharmacology and Therapeutics 08/2011; 35(3):301-4. · 1.35 Impact Factor
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    ABSTRACT: The antiparasitic ivermectin is of particular concern to regulatory agencies. Ivermectin can reach the environment through the direct emission of dung from livestock on pasture and via manure application on agricultural lands. A semifield study was conducted for assessing the ivermectin dynamic in runoff and drainage waters from dung-treated soils placed on experimental trays. The experiment was conducted under natural Mediterranean conditions. Realistic pasture and arable land applications were assessed using dung of treated animals and compared with a positive control (spraying the ivermective solution without dung). Similar concentrations were obtained in all three treatments for drainage waters, with values ranging from <5-10 to about 20 ng/l. However, strong treatment-related variation was observed in runoff waters, with the highest concentrations found in the spray treatment (9-188 ng/l), followed by the arable land (<5-88 ng/l) scenario, and concentrations not exceeding 6 ng/l in the pasture scenario. Ivermectin levels in runoff particles were up to 1,660 and 5,890 ng/kg dry weight for the pasture (I1) and arable land (I2) scenarios, respectively. Ivermectin was only detected in the drainage and runoff waters collected in the first rainfall events after treatment. The measured concentrations in water (0.006-0.118 ng/ml) and runoff particles (0.052-5.89 ng/mg dry suspended matter) are orders of magnitude higher than those provoking effects on aquatic and benthonic communities under experimental and mesocosm conditions, suggesting a clear risk for aquatic systems in the vicinity of pasture areas of treated animals or arable soil fertilized with its manure.
    Environmental Science and Pollution Research 03/2011; 18(7):1194-201. · 2.76 Impact Factor
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    ABSTRACT: A study about the influence of administration time on pharmacokinetics of Cyproterone acetate in rabbits was performed. Thirty animals were distributed in six groups, each corresponding to a different time: 2, 6, 10, 14, 18 and 22 hours after light onset (HALO). Rabbits received a single intravenous administration of 4 mg kg-1 Cyproterone acetate. Blood samples were taken and processed by high performance liquid chromatography. Plasmatic data were fitted to a biexponential equation. Concentration at zero time (Co), concentration at zero time extrapolated from the distribution phase (A), hybrid constant for distribution phase and its half life, volume of the central compartment (Vc), volume of distribution at steady state (Vss), constants for transferring the drug from the central compartment to the exterior (K10) and from the central to the peripheral compartment presented chronobiological variations (p < 0.05) and were fitted to a cosine equation. The following parameters adjusted to circadian rhythms: Co (Acrophase: 1.72 HALO); A (Acrophase: 4.09 HALO); Vc (Acrophase: 11.92 HALO); Vss (Acrophase: 10.12 HALO) and K10 (Acrophase: 3.59 HALO). It was concluded that pharmacokinetics of intravenously injected CPA in rabbits would behave in a different, though predictable, manner according to the animal's biological clock.
    Biological Rhythm Research 08/2010; October 2001(Vol. 32):401-411. · 0.47 Impact Factor
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    ABSTRACT: Buffalo breeding system has a great economic importance in South-America, principally in marginal or sub-tropical lands. The therapeutic recommendations applied to a single ruminant species are extrapolated to others but important differences among those were recognized. Marbofloxacin bolus is indicated in the treatment of neonatal gastroenteritis caused by Escherichia coli, in calves (25-50kg). The aim of this study was determined the pharmacokinetic behaviour of marbofloxacin after oral administration, as bolus, following the label approved recommendations to cattle. One bolus (50 mg) was administered in two clinically healthy buffaloes (two days-old, 48-50kg). Plasma concentrations of the marbofloxacin were determined by a HPLC/u.v. method. After oral administration, the values obtained were: tmax=0.5-6h, Cmax= 1.19-0.04μg/mL, AUCt=1.57-0.38μg·h/mL and MRTt= 3.34-6.92h, for calves 1 and 2 respectively. Fluoroquinolones act by concentration dependant killing mechanism, so high plasma concentration initially is important. For this reason, the recommended dose of 1mg/kg is inadequate in buffaloes.
    Italian Journal of Animal Science. 01/2010;
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    ABSTRACT: Marbofloxacin is a synthetic, bactericidal antimicrobial, belonging to the fluoroquinolone group which acts by inhibition of DNA gyrase and those acts by concentration dependant killing mechanism, so high plasma concentration initially is important. This drug is a fluoroquinolone developed exclusively for veterinary use, and exhibit high bactericidal activity against a broad spectrum of aerobic gram-negative, some gram-positive bacteria and Mycoplasma spp. The pharmacokinetic behaviour of marbofloxacin was investigated after intravenous (2 mg/kg) in five clinically healthy buffaloes (10 days-old). Plasma concentrations of the marbofloxacin were determined by a HPLC/ u.v. method. After intravenous administration, marbofloxacin in buffaloes was characterized by a AUC = 8,42±3,71 μg·h/ml, a large volume of distribution (Vss=1.59±0.55 L/kg) and a long persistence with an elimination half-life (t&frac12;λ) of 4.6±0,31 h, and MRT 5,90±0,57h. Furthermore, marbofloxacin in buffaloes was characterized by a relatively low total body clearance (Cl) of 0.28±0.12 L/kg·h.
    Italian Journal of Animal Science 01/2010; · 0.79 Impact Factor
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    ABSTRACT: Sulfamethazine is a sulfonamide that presents a broad spectrum of activity, including Gram-positive and Gram-negative bacteria, Chlamydia spp. and some protozoa and it commonly used in ruminants. The aim of our work was to study the possible inter-species differences in the pharmacokinetic behavior and pharmacokinetic/ pharmacodynamic(PK/PD) integration of sulfamethazine after intravenous administration in buffalo and bovine. A single intravenous dose of 60 mg/kg was administered to six bovine and five buffalo (3-4 month old and weighting 120±15kg). Plasma concentrations of sulfamethazine were determined by high performance liquid chromatography. Differences between bovine and buffalo calves were found in t&frac12;λ (buffaloes: t1/2λ =6.17±0.58h; bovine t1/2λ=7.46±1.05h), Cl (buffaloes: 45.31ml/h·kg; bovines 30.34ml/h·kg). As a consequence of the lower clearance in bovines, the AUC and t&frac12;λ values were higher in this species. Important differences between bovine and buffalo exist for microorganisms that have a MIC value<32μg/ml related to time over minimum inhibitory concentration and weighted AUC.
    Italian Journal of Animal Science. 01/2010;
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    ABSTRACT: Ivermectin is a worldwide used antiparasitic compound acting against both endo- and ecto parasites of livestock. Ivermectin can reach the environment through the direct emission of dung from livestock on pasture and via manure application on agricultural lands. Due to its very high acute toxicity to many invertebrates, especially to D. magna, the excretion profile of ivermectin in dung after application is essential for assessing its potential effects on terrestrial and aquatic ecosystems. The aim of this article is to characterize the excretion profile, comparing plasma and dung levels, after a single subcutaneous dose to cattle, to be used in environmental risk assessment. The cumulative curve of excreted ivermectin was used to calculate the PEC dung in manure to be used as fertilizer. The potential hazard for dung fauna, aquatic and soil organism is presented through the combination of toxicity and excretion levels. Three hazard levels, offering the relevant information to veterinarians prescribing the drug, are presented.
    Soil & Sediment Contamination - SOIL SEDIMENT CONTAM. 01/2009; 18(5):564-575.
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    ABSTRACT: The aim of this work was to study the pharmacokinetic behavior and the inhibitory effect of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities of chlorpyrifos (CPF) in steer cattle after pour-on administration. Determination of cholinesterase activity in plasma and erythrocyte was carried out according to Ellman kinetic method. CPF was analyzed by gas chromatography. AChE was the predominant form of cholinesterase analyzed, with low levels of BChE in plasma. Following the treatment with CPF, the maximum inhibitory effect on AChE or BChE were 50.88 +/- 11.57 and 42.66 +/- 12.01%, respectively. The chlorpyrifos plasma concentrations observed were low and they presented a high variability. Chlorpyrifos peak plasma concentration (10.42 +/- 4.76 micro g/L) was reached at 8.42 +/- 13.97 h. The pesticide was not detected in plasma after 48 h post treatment. The values of area under the curve (AUC) were 118.48 +/- 87.46 micro g x h/L and mean resistance time (MRT) were 13.38 +/- 10.41 h. The pour-on exposure to the organophosphate chlorpyrifos significantly reduced AChE and BChE activity in steer cattle and the recovery was not reached on 50 days post-treatment.
    Journal of Environmental Science and Health Part B Pesticides Food Contaminants and Agricultural Wastes 07/2008; 43(5):405-9. · 1.10 Impact Factor
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    ABSTRACT: Sulphonamides are still being used widely, influenced by the low cost and the efficacy against many common bacterial infections, since they present a broad spectrum of activity. The aim of this study was to determine the effect of age on the pharmacokinetic/pharmacodynamics (PK/PD) integration of intravenous sulfamethazine (60 mg/kgbw) in cattle, and the possible therapeutic outcomes. Six healthy female calves, at the age of one, three, seven and fifteen weeks were used. Normality analysis was assessed with the Shapiro-Wilk test. Non-parametric tests for paired data were used. Plasma concentrations were quantified using HPLC/uv. Differences were found between one-three-weeks-old calves and seven-fifteen-weeks-old calves, in pharmacokinetic parameters (clearance, area under the concentration-time curve and elimination half-life) and in the PK/PD integration. The ratios obtained in PK/PD integration (T>MIC, WAUC) confirm that it is necessary to apply twice the dose of sulfamethazine in > or = 7 weeks-old cattle to reach a satisfactory dosage regimen (MIC > or = 32 microg/mL).
    Veterinary Research Communications 05/2008; 32(7):509-19. · 1.08 Impact Factor
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    ABSTRACT: This study compared pharmacokinetic profiles in cattle dosed subcutaneously with two different formulations of enrofloxacin (5% and 10%) at a dose of 5 mg/kg. Plasma concentrations of enrofloxacin and its active metabolite, ciprofloxacin, were determined by a HPLC/u.v. method. The pharmacokinetic parameters of enrofloxacin and its metabolite were similar in both injectable formulations. Enrofloxacin peak plasma concentration (5%: 0.73 +/- 0.32; 10%: 0.60 +/- 0.14 microg/mL) was reached at 1.21 +/- 0.52 and 1.38 +/- 0.52 h to 5 and 10%, respectively. The terminal half-live and area under curve were 2.34 +/- 0.46 and 2.59 +/- 0.46 h, and 3.09 +/- 0.81 and 2.93 +/- 0.58 microg x h/mL, to 5 and 10%, respectively. The AUC/MIC(90) and Cmax/MIC(90) ratios for both formulations exceed the proposed threshold values for optimized efficacy and minimized resistance development whilst treating infections or septicaemia caused by P. multocida and E. coli.
    Veterinary Research Communications 05/2008; 32(4):275-9. · 1.08 Impact Factor
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    ABSTRACT: The pharmacokinetic behavior of marbofloxacin was studied in goats after single-dose subcutaneous (SC) administration of 2mg/kg bodyweight. Drug concentration in plasma was determined by high performance liquid chromatography and the data obtained were subjected to non-compartmental kinetic analysis. Marbofloxacin peak plasma concentration (C(max)=1.77+/-0.24microg/mL) was reached 1.25+/-0.50h (T(max)) after SC administration. The elimination half-life (t(1/2beta)) and area under curve (AUC) were 5.74+/-1.21h and 8.15 vs 2.33microg h/mL, respectively. Taking into account the values obtained for the efficacy indices, it was concluded that a SC dose of 2mg/kg/24h of marbofloxacin could be adequate to treat infections caused by high susceptible bacteria like Escherichia coli or Salmonella spp.
    The Veterinary Journal 10/2007; 174(2):425-7. · 2.42 Impact Factor
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    ABSTRACT: Six donkeys each received 2 mg/kg marbofloxacin as a 10 per cent aqueous solution administered intravenously. Principal pharmacokinetic parameters were determined and two efficacy indices were computed by using pharmacokinetic parameters and selected mic90 values of marbofloxacin against pathogenic equine strains to predict the efficacy of the drug at this dose. The pharmacokinetics of marbofloxacin in donkeys was characterised by a large mean volume of distribution at a steady state (1.15 [0.09] l/kg) and a long mean (sd) elimination half-life of 9.24 (1.96) hours. It was also characterised by a relatively slow total body clearance of 0.10 (0.02) l/kg/hour, slower than in horses. Using mic90 values of marbofloxacin against pathogenic equine strains with a daily dose of 2 mg/kg, appropriate values of efficacy indicators were obtained only for Enterobacteriaceae. Daily intravenous doses of 0.33, 2.62 and 20 mg/kg were calculated for evaluation in clinical trials of infections due to Enterobacteriaceae, Staphylococcus aureus and Streptococci, respectively.
    The Veterinary record 08/2007; 161(4):133-6. · 1.80 Impact Factor
  • Journal of Veterinary Pharmacology and Therapeutics 07/2007; 30(3):271-4. · 1.35 Impact Factor
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    ABSTRACT: The objectives of this work were to compare the pharmacokinetics of erythromycin administered by the intramuscular (i.m.) and intravenous (i.v.) routes between nonlactating and lactating goats and to determine the passage of the drug from blood into milk. Six nonpregnant, nonlactating and six lactating goats received erythromycin by the i.m. (15 mg/kg) and the i.v. (10 mg/kg) routes of administration. Milk and blood samples were collected at predetermined times. Erythromycin concentrations were determined by microbiological assay. Results are reported as mean +/- SD. Comparison of the pharmacokinetic profiles between nonlactating and lactating animals after i.v. administration indicated that significant differences were found in the mean body clearance (8.38 +/- 1.45 vs. 3.77 +/- 0.83 mL/kg x h respectively), mean residence time (0.96 +/- 0.20 vs. 3.18 +/- 1.32 h respectively), area under curve from 0 to 12 h (AUC(0-12)) (1.22 +/- 0.22 vs. 2.76 +/- 0.58 microg x h/mL respectively) and elimination half-life (1.41 +/- 1.20 vs. 3.32 +/- 1.34 h); however, only AUC(0-12) showed significant differences after the i.m. administration. Passage of erythromycin in milk was high (peak milk concentration/peak serum concentration, 2.06 +/- 0.36 and AUC(0-12milk)/AUC(0-12serum),6.9 +/- 1.05 and 2.37 +/- 0.61 after i.v. and i.m. administrations respectively). We, therefore, conclude that lactation affects erythromycin pharmacokinetics in goats.
    Journal of Veterinary Pharmacology and Therapeutics 03/2007; 30(1):80-5. · 1.35 Impact Factor
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    ABSTRACT: Ketamine is a short-acting dissociative anaesthetic for chemical restraint and surgical anaesthesia in domestic and non-domestic animals. The present study was designed to determine the pharmacokinetics of a single dose of ketamine (10 mg/kg) after intramuscular (i.m.) administration to young ostriches premedicated with romifidine. Ketamine was rapidly absorbed after i.m. administration. Maximal ketamine concentration (C(max)) of 2.93 +/- 0.61 microg/ml was reached at 12.5 +/- 2.50 min and thereafter ketamine concentrations decreased rapidly. The elimination half-life (t(1/2 z)) obtained was 62.37 +/- 17.37 min and mean residence time (MRT) was 77.33 +/- 19.12 min. The area under the curve (AUC) was 114.19 +/- 15.76 microg x min/ml.
    Journal of Veterinary Medicine Series A 03/2007; 54(1):48-50. · 0.93 Impact Factor
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    ABSTRACT: This study reports on the administration of a single dose of marbofloxacin (2 mg/kg) to five adult Eurasian buzzards (Buteo buteo) by the intraosseous (IO) route, which has been proposed as a rapid and efficient means for the parenteral delivery of antimicrobial drugs. The drug was rapidly absorbed. Peak marbofloxacin concentration (C(max)) in plasma and area under the concentration-time curve (AUC) of 1.92+/-0.78 microg/mL and 8.53+/-2.73 microg h/mL, respectively. The time marbofloxacin remained in the plasma after IO administration was relatively short (elimination half-life, t(1/2beta)=4.91+/-0.65 h; mean residence time (MRT)=5.38+/-0.57 h). Single dose marbofloxacin gave values for C(max)/minimum inhibitory concentration (MIC) of 19.2 and an AUC/MIC value of 85.3h after IO administration. The IO route appears to be practical and effective for the rapid delivery of marbofloxacin to buzzards.
    The Veterinary Journal 06/2006; 171(3):551-5. · 2.42 Impact Factor

Publication Stats

206 Citations
57.82 Total Impact Points

Institutions

  • 1988–2013
    • Complutense University of Madrid
      • • Department of Toxicology and Pharmacology
      • • Departamento de Farmacología
      • • Facultad de Veterinaria
      Madrid, Madrid, Spain
  • 2011
    • Temuco Catholic University
      • Escuela de Medicina Veterinaria
      Temuco, Region de la Araucania, Chile
  • 2003–2007
    • University of Buenos Aires
      • Faculty of Veterinary Sciences
      Buenos Aires, Buenos Aires F.D., Argentina
  • 1998–2007
    • Universidad Nacional del Litoral
      • Faculty of Veterinary Science FCV
      Santa Fe de la Vera Cruz, Provincia de Santa Fe, Argentina